The hypothesis of this proposal is that optical coherence microscopy (OCM), a combination of OCT with confocal microscopy, can enable cellular resolution endoscopic imaging of tissue morphology, thereby dramatically advancing the capabilities of either technique for endoscopic detection of early stage neoplasms. An endoscopic "optical biopsy" technique that allows for real time, in vivo imaging of precancerous changes at the cellular level would allow image guidance of traditional excisional biopsy, potentially reducing sampling error and improving sensitivity. The specific aims are: 1) Develop optical coherence microscopy (OCM) technology for cellular imaging of unstained tissues. 2) Investigate OCM for detecting early neoplastic cellular alterations in human tissues through ex vivo clinical imaging studies. 3) Develop miniaturized flexible endoscopes for OCM imaging based on micro-electro-mechanical systems (MEMS) scanning technology. 4) Validate flexible OCM endoscopes through in vivo animal imaging experiments. These studies combined seek to demonstrate fundamental new advances for endoscopic detection of early stage neoplasms.